tbuckley/cabot-search huggingface dataset:
Abstract ND03: Discovery of ARV-766, an androgen receptor degrading PROTAC® for the treatment of men with metastatic castration resistant prostate cancer
Authors: Larry Snyder, S H. Lee, T K. Neklesa, X Chen, H Dong, C Ferraro, D A. Gordon, J Macaluso, J Pizzano, J Wang, R R. Willard, N Vitale, R Peck, M D. Moore, C M. Crews, J Houston, A P. Crew, I Taylor
Journal: Cancer Research (2023)

Abstract Prostate cancer is the second leading cause of cancer death in men in the United States. The androgen receptor (AR) plays critical roles in both early disease and advanced prostate cancer. Current therapeutic approaches targeting the androgen/AR axis are initially effective, but castration resistant prostate cancer (CRPC) inevitably develops. CRPC is linked with increased AR activity via gene overexpression, amplification, and gain-of-function mutations. To address these mechanisms of AR-dependent prostate tumor growth, we have developed a novel therapeutic agent, ARV-766, a proteolysis targeting chimera (PROTAC®) that induces a protein-protein interaction between the AR and specific E3 ubiquitin ligase complexes, leading to the ubiquitination of AR and its subsequent degradation via the proteasome. In vitro, ARV-766 degrades AR in various prostate cancer cell lines, including those harboring resistance-conferring, clinically relevant point mutations, with a half-maximal degradation concentration (DC50) of &amp;lt;1 nM in wild type VCaP. Importantly ARV-766 also maintains potency against the AR L702H mutant, which has been associated with resistance to some AR antagonists. In vivo, ARV-766 is orally bioavailable and robustly degrades AR with a &amp;gt;90% observed maximum degradation (Dmax) at efficacious doses. ARV-766 significantly and dose-dependently inhibits tumor growth in murine LNCaP and VCaP xenograft models, including an enzalutamide-insensitive non-castrated VCaP model. These preclinical data supported the clinical development of ARV-766 for the treatment of men with metastatic CRPC. Selected pre-clinical data along with the chemical structure of ARV-766 will be presented. Citation Format: Larry Snyder, S H. Lee, T K. Neklesa, X Chen, H Dong, C Ferraro, D A. Gordon, J Macaluso, J Pizzano, J Wang, R R. Willard, N Vitale, R Peck, M D. Moore, C M. Crews, J Houston, A P. Crew, I Taylor. Discovery of ARV-766, an androgen receptor degrading PROTAC® for the treatment of men with metastatic castration resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr ND03.
Laparoscopic endoscopic cooperative surgery for the duodenal neuroendocrine tumor: A single-center case series (How I Do It)
Authors: Chun-Guang Guo, Hoi-Ioi Ng, Yong Liu, Chong-Yuan Sun, Xiao-Jie Zhang, Dong-Bing Zhao, Gui-Qi Wang
Journal: International Journal of Surgery (2023)

Duodenal neuroendocrine tumors (D-NETs) are uncommon. The surgical treatment for D-NETs was in debate. Laparoscopic and endoscopic cooperative surgery (LECS) is a promising approach for treating gastrointestinal tumors. The study aimed to evaluate the feasibility and safety of LECS for D-NETs. Meanwhile, the authors described the details of the LECS technique.All patients diagnosed with D-NETs underwent LECS between September 2018 and April 2022 were retrospectively reviewed. The endoscopic procedures were performed with endoscopic full-thickness resection. The defect was manually closed under the surveillance of the laparoscopy.A total of seven patients were enrolled, including three men and four women. The median age was 58 years (ranging from 39-65). Four tumors were located in the bulb and three in the second portion. All cases were diagnosed as NET with grade G1. The tumor depth was pT1 in two cases and pT2 in five cases. The median specimen size and the tumor size were 22 mm (ranging from 10-30) and 8.0 mm (ranging from 2.3-13.0), respectively. En-bloc resection and curative resection rates are 100 and 85.7%, respectively. There were no severe complications. Until 1 June 2022, there was no recurrence. The median follow-up was 9.5 months (range, 1.4-45.1).LECS with endoscopic full-thickness resection is a reliable surgical procedure. The minimally invasive advantages of LECS enable more individualized treatment options for a specific group. Limited by the length of observation, the long-term performance of LECS for D-NETs requires additional investigation.
Effect of early achievement of energy target by different nutritional support strategies on nosocomial infections in patients undergoing major abdominal surgery: a secondary analysis of two randomized clinical trials
Authors: Xuejin Gao, Li Zhang, Yupeng Zhang, Da Zhou, Tingting Gao, Yuxiu Liu, Gang Jin, Kunhua Wang, Yanbing Zhou, Qiang Chi, Hua Yang, Mengbin Li, Jianchun Yu, Huanlong Qin, Yun Tang, Xiaoting Wu, Guoli Li, Xinying Wang
Journal: International Journal of Surgery (2023)

Background: The effect of early achievement of energy targets using different nutritional support strategies in patients undergoing major abdominal surgery is unclear. This study determined the impact of early achievement of energy targets on the incidence of nosocomial infections in patients undergoing major abdominal surgery. Methods: This was a secondary analysis of two open-label randomized clinical trials. Patients from the general surgery department of 11 academic hospitals in China undergoing major abdominal surgery and at nutritional risk (Nutritional risk screening 2002≥3) were divided into two groups based on whether they met the 70% energy targets, the early achievement of energy target (521 EAET) and non-achievement of energy target (114 NAET) groups. The primary outcome was the incidence of nosocomial infections between postoperative day 3 and discharge, and the secondary outcomes were actual energy and protein intake, postoperative noninfectious complications, intensive care unit admission, mechanical ventilation, and hospital stay. Results: Overall, 635 patients (mean [standard deviation, SD]) age, 59.5 [11.3] years) were included. The EAET group received more mean energy between days 3 and 7 than the NAET group (22.7±5.0 kcal/kg/d vs. 15.1±4.8 kcal/kg/d; P &lt;0.001). The EAET group had significantly fewer nosocomial infections than the NAET group (46/521[8.8%] versus 21/114[18.4%]; risk difference, 9.6%; 95% confidence interval [CI], 2.1%-17.1%; P =0.004). A significant difference was found in the mean (SD) number of noninfectious complications between the EAET and NAET groups (121/521[23.2%] vs. 38/114[33.3%]; risk difference, 10.1%; 95%CI, 0.7%-19.5%; P =0.024). The nutritional status of the EAET group was significantly improved at discharge compared with the NAET group ( P &lt;0.001), and other indicators were comparable between groups. Conclusion: Early achievement of energy targets was associated with fewer nosocomial infections and improved clinical outcomes, regardless of the nutritional support strategy (early enteral nutrition alone or combined with early supplemental parenteral nutrition).
Effectiveness and safety of central pancreatectomy in benign or low-grade malignant pancreatic body lesions: a systematic review and meta-analysis
Authors: Shiyuan Bi, Yingyu Liu, Wanlin Dai, Liwei Pang, Shaojie Yang, Yuting Zheng, Xiaolin Zhang, Shuodong Wu, Jing Kong
Journal: International Journal of Surgery (2023)

Background: The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased. Objectives: The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases. Methods: The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software. Results: Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time (P<0.0001), less blood loss (P<0.01), overall and clinically relevant pancreatic fistula (P<0.0001), postoperative hemorrhage (P<0.0001), reoperation (P=0.0196), delayed gastric emptying (P=0.0096), increased hospital stay (P=0.0002), intra-abdominal abscess or effusion (P=0.0161), higher morbidity (P<0.0001) and severe morbidity (P<0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency (P<0.01), and new-onset and worsening diabetes mellitus (P<0.0001) than DP. Conclusions: CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.
Noninvasive imaging evaluation of peritoneal recurrence and chemotherapy benefit in gastric cancer after gastrectomy：a multicenter study
Authors: Zepang Sun, Wei Wang, Weicai Huang, Taojun Zhang, Chuanli Chen, Qingyu Yuan, Yan Chen, Kangneng Zhou, Zhen Han, Hao Feng, Hao Chen, Xiaokun Liang, Yanfeng Hu, Jiang Yu, Hao Liu, Lequan Yu, Yikai Xu, Guoxin Li, Yuming Jiang
Journal: International Journal of Surgery (2023)

Background: Peritoneal recurrence (PR) is the predominant pattern of relapse after curative-intent surgery in gastric cancer (GC) and indicates a dismal prognosis. Accurate prediction of PR is crucial for patient management and treatment. The authors aimed to develop a noninvasive imaging biomarker from computed tomography (CT) for PR evaluation, and investigate its associations with prognosis and chemotherapy benefit. Methods: In this multicenter study including five independent cohorts of 2005 GC patients, the authors extracted 584 quantitative features from the intratumoral and peritumoral regions on contrast-enhanced CT images. The artificial intelligence algorithms were used to select significant PR-related features, and then integrated into a radiomic imaging signature. And improvements of diagnostic accuracy for PR by clinicians with the signature assistance were quantified. Using Shapley values, the authors determined the most relevant features and provided explanations to prediction. The authors further evaluated its predictive performance in prognosis and chemotherapy response. Results: The developed radiomics signature had a consistently high accuracy in predicting PR in the training cohort (area under the curve: 0.732) and internal and Sun Yat-sen University Cancer Center validation cohorts (0.721 and 0.728). The radiomics signature was the most important feature in Shapley interpretation. The diagnostic accuracy of PR with the radiomics signature assistance was improved by 10.13–18.86% for clinicians (P<0.001). Furthermore, it was also applicable in the survival prediction. In multivariable analysis, the radiomics signature remained an independent predictor for PR and prognosis (P<0.001 for all). Importantly, patients with predicting high risk of PR from radiomics signature could gain survival benefit from adjuvant chemotherapy. By contrast, chemotherapy had no impact on survival for patients with a predicted low risk of PR. Conclusion: The noninvasive and explainable model developed from preoperative CT images could accurately predict PR and chemotherapy benefit in patients with GC, which will allow the optimization of individual decision-making. Export
Meta-analysis of post-transcatheter aortic valve replacement outcomes in patients with cardiac amyloidosis and aortic stenosis
Authors: Vikash Jaiswal, Amey Joshi, Angela Ishak, Megha Nataraj, Song P. Ang, Nida Khan, Farshid Daneshvar, Victor H. Aguilera-Alvarez, Deepak Verma, Abhigan B. Shrestha, Prachi Sharma
Journal: International Journal of Surgery (2023)

Jaiswal, Vikash MD; Joshi, Amey MBBS; Ishak, Angela MD; Nataraj, Megha; Ang, Song Peng MD; Khan, Nida MBBS; Daneshvar, Farshid; Aguilera-Alvarez, Victor Hugo MD, MPH; Verma, Deepak MBBS; Shrestha, Abhigan Babu MBBS; Sharma, Prachi MD, DM Author Information
Tricuspid valve repair concomitant with mitral valve surgery: a systematic review and meta-analysis
Authors: Kang Yi, Wei Wang, Jianguo Xu, Xin Zhang, Wenxin Wang, Chengfei Liu, Xinyao Li, Tao You
Journal: International Journal of Surgery (2023)

Uncertainties persist about whether to aggressively and effectively treat tricuspid regurgitation (TR) during mitral valve (MV) surgery.
The experience of neoadjuvant chemotherapy versus upfront surgery in resectable pancreatic cancer: a cross sectional study
Authors: Yung-Yeh Su, Ying-Jui Chao, Chih-Jung Wang, Ting-Kai Liao, Ping-Jui Su, Chien-Jui Huang, Nai-Jung Chiang, Yu-Ting Yu, Hong-Ming Tsai, Li-Tzong Chen, Yan-Shen Shan
Journal: International Journal of Surgery (2023)

Upfront resection (UR) followed by adjuvant chemotherapy remains the standard treatment for resectable pancreatic cancer. There is increasing evidence suggesting favourable outcomes toward neoadjuvant chemotherapy (NAC) followed by surgery.All clinical staging with resectable pancreatic cancer patients treated at a tertiary medical centre from 2013 to 2020 were identified. The baseline characteristics, treatment course, surgery outcome and survival results of UR or NAC were compared.Finally, in 159 resectable patients, 46 patients (29%) underwent NAC and 113 patients (71%) received UR. In NAC, 11 patients (24%) did not receive resection, 4 (36.4%) for comorbidity, 2 (18.2%) for patient refusal and 2 (18.2%) for disease progression. In UR, 13 patients (12%) were unresectable intraoperatively; 6 (46.2%) for locally advanced and 5 (38.5%) for distant metastasis. Overall, 97% of patients in NAC and 58% of patients in UR completed adjuvant chemotherapy. As of data cut-off, 24 patients (69%) in NAC and 42 patients (29%) in UR were still tumour free. The median recurrence-free survival in NAC, UR with adjuvant chemotherapy and without adjuvant chemotherapy were 31.3 months (95% CI, 14.4-not estimable), 10.6 months (95% CI, 9.0-14.3) and 8.5 months (95% CI, 5.8-11.8), P =0.036; and the median overall survival in each group were not reached (95% CI, 29.7-not estimable), 25.9 months (95% CI, 21.1-40.5) and 21.7 months (12.0-32.8), P =0.0053. Based on initial clinical staging, the median overall survival of NAC was not significantly different from UR with a tumour less than or equal to 2 cm, P =0.29. NAC patients had a higher R0 resection rate (83% versus 53%), lower recurrence rate (31% versus 71%) and harvested median number lymph node (23 versus 15).This study demonstrates that NAC is superior to UR in resectable pancreatic cancer with better survival.
Incidence and cost of clinically recognized vertebral fracture in urban China is dramatically increasing
Authors: Zhenlin Zhang
Journal: International Journal of Surgery (2023)

Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China, 200233 Assistance with the study: None. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding Author. Address: Shanghai 6th Peoples Hospital Affiliated to Shanghai Jiao Tong University, CHINA. Phone: +86-021-64369181. Fax: +86-021-64369181. E-mail address: [email protected](Z. Zhang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Impact of adjuvant therapy in patients with invasive intraductal papillary mucinous neoplasms of the pancreas: an international multicenter cohort study
Authors: Munseok Choi, Shin-E Wang, Joon Seong Park, Hyung Sun Kim, Sung Hoon Choi, Jin Ho Lee, Jae Uk Chong, Yuichi Nagakawa, Keita Wada, Yoshiharu Nakamura, Hiroki Sunagawa, Bobby VM Dasari, Cheng-Ming Peng, Lee Lip Seng, Heiner Wolters, Unenbat Gurbadam, Byoung UK Park, Emily Winslow, Thomas Fishbein, Jason Hawksworth, Pejman Radkani, Chang Moo Kang
Journal: International Journal of Surgery (2023)

Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN.From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted.A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group ( P =0.003), but overall survival (OS) was not ( P =0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P =0.402; stage II, P =0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P =0.481; N+, P =0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408-6.772, P <0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247-3.395, P =0.005) were identified as adverse prognostic factors in resected invasive IPMN.The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended.
Prognostic value of preoperative serum cystatin-C level for non-metastatic renal cell carcinoma—correspondence
Authors: Yaxiong Tang, Yunfei Xiao, Kaige Pei, Linghao Meng, Xiang Li
Journal: International Journal of Surgery (2023)

Tang, Yaxiong MD; Xiao, Yunfei MD; Pei, Kaige MD; Meng, Linghao MD; Li, Xiang MD Author Information
Neutrophil extracellular trap interfering therapy: a potential therapeutic option for cancers?
Authors: Dhivyadharshini Gajendran, Vishnu Priya Veeraraghavan, Krishna Mohan Surapaneni, Lavina Prashar, Ullas Mony
Journal: International Journal of Surgery (2023)

Gajendran, Dhivyadharshini BDS; Veeraraghavan, Vishnu Priya PhD; Surapaneni, Krishna Mohan PhD, MHPE, FRSC; Prashar, Lavina MD; Mony, Ullas PhD Author Information
Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia: a multicenter cohort study
Authors: Monica EW Derks, Maarten te Groen, Charlotte P Peters, Gerard Dijkstra, Annemarie C de Vries, Tessa EH Romkens, Carmen S Horjus, Nanne KH de Boer, Willem A Bemelman, Iris D Nagtegaal, Lauranne AAP Derikx, Frank Hoentjen
Journal: International Journal of Surgery (2023)

Background: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia (HGD) or colorectal cancer (CRC)). We aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD and (2) identify factors associated with treatment choice. Material and methods: In this retrospective multicenter cohort study, we used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic AN between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine&Gray’s subdistribution hazard models were used to assess adjusted subdistribution hazard ratios (asHR) for metachronous neoplasia and associations with treatment choice. Results: We included 189 patients (HGD n=81; CRC n=108). Patients were treated with proctocolectomy (n=33), (sub)total colectomy (n=45), partial colectomy (n=56) and endoscopic resection (n=38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn’s disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n=22, partial colectomy n=8, endoscopic resection n=13). We found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (asHR 4.16, 95% CI 1.64-10.54, P<0.01) compared to (sub)total colectomy. Conclusion: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance. Export
Neutrophil-to-lymphocyte ratio to estimate colorectal cancer liver metastasis: a commentary
Authors: Kaina Wang, Yujing Chen, Zhonghua Nie, Jingyu Wang
Journal: International Journal of Surgery (2023)

aZhejiang Chinese Medical University, Hangzhou, Zhejiang, China bZhejiang Chinese Medical University, Hangzhou, Zhejiang, China cThe First Hospital of Jiaxing/Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China dDepartment of Pathology, The First Hospital of Jiaxing/Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China Jingyu Wang Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: (Department of Pathology, The First Hospital of Jiaxing/Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, 314000, PR China. E-mail address: [email protected] (J. Wang). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/
Optimizing the Utility of Anorectal Manometry for Diagnosis and Therapy: A Roundtable Review and Recommendations
Authors: Satish S.C. Rao, Nitin K. Ahuja, Adil E. Bharucha, Darren M. Brenner, William D. Chey, Jill K. Deutsch, David C. Kunkel, Baharak Moshiree, Leila Neshatian, Robert M. Reveille, Gregory S. Sayuk, Jordan M. Shapiro, Eric D. Shah, Kyle Staller, Steven D. Wexner, Jason R. Baker
Journal: Clinical Gastroenterology and Hepatology (2023)

Anorectal manometry (ARM) is a comprehensive diagnostic tool for evaluating patients with constipation, fecal incontinence, or anorectal pain; however, it is not widely utilized for reasons that remain unclear. The aim of this roundtable discussion was to critically examine the current clinical practices of ARM and biofeedback therapy by physicians and surgeons in both academic and community settings.
Longitudinal Monitoring of Circulating Tumor DNA From Plasma in Patients With Curative Resected Stages I to IIIA EGFR-Mutant Non–Small Cell Lung Cancer
Authors: Hyun-Ae Jung, Bo Mi Ku, Yeon Jeong Kim, Sehhoon Park, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Jong Ho Cho, Hong Kwan Kim, Yong Soo Choi, Yoon-La Choi, Sun Hye Shin, Byeong-Ho Jeong, Sang-Won Um, Hojoong Kim, Kyunga Kim, Myung-Ju Ahn, Jingook Kim
Journal: Journal of Thoracic Oncology (2023)